tbuckley/cabot-search huggingface dataset:
A rare subtype of the glial tumor with <i>H3F3B</i> p.K28I in Chinese adult diffuse midline gliomas.
Authors: Feng Ding, Ningning Luo, Tiantian Han, Didi Guo, Guanghua Lu, Fanfeng Bu
Journal: Journal of Clinical Oncology (2022)

e14012 Background: Diffuse midline gliomas (DMGs) with H3 K27 altered are extremely aggressive WHO grade IV tumors, with no significant therapeutic progress made in the past. DMGs with H3 K27 altered have been classified as a rare subtype of glial tumor according to 2021 WHO Classification of CNS Tumors. K27M mutation always occurs in the H3F3A gene or HISTIH3B/C gene, and the majority of DMGs harbor H3 K27M-mutation. Studies have been reported that systematic in vitro modification of the lysine 27 predicts K27I as the only substitution other than K27M to result in a repressive effect on H3K27me3. Herein, we reported two adult patients with DMGs harboring somatic H3-K27I mutation. It is important to identify H3 K27-mutation accurately for accurate diagnosis, prognostication, and also for treatment selection. Methods: Next-generation sequencing (NGS) 539-gene panel (Simceredx) profiling was performed using postoperative tissue. The molecular characteristics, K3 K27 mutation types, and other co-mutations were also evaluated. Results: Patient one was a 36-year-old female. Magnetic resonance images (MRI) of the brain were performed and showed the pons tumor in the brainstem. Postoperative pathology showed astrocytoma (WHO Grade II) with diffuse slightly dense cells. NGS results showed that the patient was carried H3F3B exon2 p.K27I (allele frequency, AF 57.64%), TP53 exon7 p.M237I (AF 80.27%). Patient two was a 44-year-old male and was diagnosed with spinal cord glioma, WHO grade III. NGS panel profiling was performed and H3F3B exon2 p.K27I (AF 30.46%), ATRX exon9 p.S1173* (AF 75.23%), KRAS exon2 p.G12A(AF 38.11%) and NF1 intron42 c.6580-1G &gt; A(AF 36.44%) were identified. Conclusions: In our study, we identified the H3F3B K27I mutation in two adult DMG patients by NGS, which expanded the detection gene spectrum of DMG patients. The type of histone H3 mutated could also predict the outcome and accurate diagnosis and glioma grading of DMG patients, which was more efficient than clinical and radiological characteristics of the tumors. Accurate genetic testing should be given more attention to those patients.
A phase II study evaluating KN026 monotherapy in patients (pts) with previously treated, advanced HER2-expressing gastric or gastroesophageal junction cancers (GC/GEJC).
Authors: Jianming Xu, Rongrui Liu, Jieer Ying, Jun Wu, Feng Ye, Nong Xu, Yanqiao Zhang, Rusen Zhao, Xiaojun Xiang, Jianhong Wang, Xiaoyan Lin, Huiting Xu, Shegan Gao, SuXia Luo, Baohong Guo, Xionghui Li, Yangzhi Su, Qian Wang
Journal: Journal of Clinical Oncology (2022)

4040 Background: Outcomes of second or later-line treatment for pts with advanced GC/GEJC remain inferior. KN026 is a novel HER2-targeted bispecific antibody composed of VH regions of trastuzumab and pertuzumab, targeting the HER2 juxtamembrane domain (IV) and the dimerization domain (II) simultaneously. KN026 has shown promising antitumor efficacy in preclinical and phase I studies. Here we present the results of KN026 monotherapy in previously treated, advanced HER2-expressing GC/GEJC. Methods: In this multi-center, single-arm, open-label, 2-cohort phase II study, adult pts with previously treated, advanced GC/GEJC were assigned into a HER2 high-level cohort (Cohort 1: IHC3+ or IHC 2+ ISH+) or a HER2 low-level cohort (Cohort 2: IHC 1+/2+ ISH- or IHC 0/1+ISH+). KN026 was given intravenously in 10 mg/kg QW, 20 mg/kg Q2W, or 30 mg/kg Q3W. Primary endpoints were objective response rate (ORR) and duration of response (DoR) assessed by investigators per RECIST 1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety outcomes. This trial is registered at ClinicalTrials.gov (NCT03925974). Results: At data cut-off (Oct. 29, 2021), 45 pts were enrolled and treated with KN026; 39 were eligible for response evaluation (25 pts in Cohort 1 and 14 pts in Cohort 2). In Cohort 1, ORR was 56% (95%CI 35%-76%) with 14 PR; the median DoR was 9.7 months (mo) (95%CI 4.2-not evaluable (NE)). At a median follow-up of 14.7 mo (95%CI 9.4-16.5), the median PFS was 8.3 mo (95%CI 4.2-11.4), and median OS was 16.3 mo (95% CI 11.0- NE). In Cohort 2, ORR was 14% (95%CI 2%-43%), with median DoR being 6.2 mo (95%CI 3.2-NE). At a median follow-up of 27.5 mo (95%CI 4.1-NE), the median PFS was 1.4 mo (95%CI 1.4-4.1), and median OS was 9.6 mo (95% CI 3.5-14.9). The table shows efficacy in Cohort 1 pts who have progressed on the prior trastuzumab treatment. KN026-related adverse events (TRAEs) were observed in 37 (82%) pts; the most common TRAEs (any grade) were increased aspartate aminotransferase (12, 27%), increased alanine aminotransferase (9, 20%), rash (7,16%), anemia (7,16%), and infusion-related reaction (7,16%). Four pts reported 5 grade 3 TRAEs, including infusion-related reaction, renal hydrocele, ureteral stenosis, increased blood pressure, and abnormal hepatic function (1 each). No grade 4 or 5 TRAEs occurred. Conclusions: KN026 monotherapy yielded promising efficacy with mild to moderate toxicities in pts with previously treated, advanced GC/GEJC. Further investigation is warranted. Clinical trial information: NCT03925974. [Table: see text]
GCT-22. OUTCOMES OF CHILDREN WITH LOCALIZED AND METASTATIC GERMINOMA TREATED WITH CHEMOTHERAPY FOLLOWED BY RADIATION THERAPY WITHOUT PRIMARY TUMOR BOOST
Authors: Inci Yaman Bajin, Jen Chun Foo, Eric Bouffet, Birgit Ertl-Wagner, Derek Tsang, Norman Laperriere, Peter Dirks, James Drake, Ute Bartels
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Response-based radiation therapy has been the approach for germinoma after chemotherapy. However, the presence of residual lesions at the end of chemotherapy did not demonstrate a negative impact on progression-free survival (PFS). Similarly, resection of residual tumors after chemotherapy did not show a survival benefit. AIM: Our study objective was to determine long-term outcomes of a cohort who received chemotherapy and radiation therapy without primary tumor boost even in the absence of complete response to chemotherapy. METHOD: This retrospective study analyzed the outcome of germinoma patients diagnosed and treated at a tertiary care center from January 2006 to December 2021. RESULTS: Twenty-nine children (14 male; median age 12.8 years) were identified. Median follow-up was 63 months (range 9-187 months). Twenty children had localized disease and tumor location was suprasellar (n= 9), pineal (n= 10), and bifocal (n= 1) while 9 children had metastatic disease at presentation. All patients completed multi-agent chemotherapy followed by either whole ventricular (WVI) (23.4 Gy) (n = 23), whole brain (WBI) (23.4 Gy) (n = 5) or craniospinal radiation (CSI) (23.4 Gy) (n= 1). Two children, who had localized disease at presentation and received WVI after chemotherapy, relapsed 9 months and 32 months after completion of treatment respectively. None of them had local relapses. Location of relapse was distant, outside (n= 1) and inside (n= 1) the radiation field. Five-year PFS was 93% and overall survival (OS) was 100%. CONCLUSION: In this limited experience, excellent 5-year PFS and OS rates were achieved with chemotherapy followed by radiation therapy delivered without primary tumor boost. This study also demonstrated the absence of local relapse despite omitting primary tumor boost in patients with localized and metastatic germinoma.
Patient- and provider-level factors associated with telehealth utilization across a multisite, multiregional cancer practice.
Authors: Joshua Pritchett, Bijan J. Borah, Ruchita Dholakia, James P. Moriarty, Hannah Ahn, Ming Huang, Nandita Khera, Mohamed Kharfan-Dabaja, Jonathan Ticku, Aaron L. Leppin, Jon Charles Tilburt, Jonas Paludo, Tufia C. Haddad
Journal: Journal of Clinical Oncology (2022)

1512 Background: In response to the COVID-19 pandemic, many cancer practices adopted telehealth, including telephone and video appointments. Following a period of initial expansion that began in March 2020, sustained telehealth integration has emerged across the Mayo Clinic Cancer Practice (MCCP) in 2021. The primary objective of this study was to identify factors associated with utilization of telehealth appointments. Methods: A cross-sectional, multi-site, retrospective analysis was conducted across MCCP – a multisite, multiregional cancer practice with tertiary referral campuses in Minnesota, Florida, and Arizona, as well as rural, community-based hospitals and clinics throughout the Upper Midwest. Multivariable models were used to examine the association of patient- and provider-level variables with telehealth utilization. Results: Outpatient appointments conducted in July – August 2019 (n = 32,932) were compared with those from 2020 (n = 33,662) and 2021 (n = 35,486). The rate of telehealth appointment utilization increased from &lt;0.01% in 2019 to 11.0% in 2020 and 14.0% in 2021. The strongest provider-level predictor of telehealth utilization was female physician provider type (OR 1.06, 95% CI 1.01 to 1.11; P = 0.0297), a trend consistently observed across career stages, practice locations and settings in 2020 and 2021. Additionally, while the rate of telehealth utilization was not significantly different at referral and community-based campuses in 2020, providers at referral campuses were significantly more likely to utilize telehealth than community-based campuses in 2021 (OR 1.1, 95% CI 1.01 to 1.12; P = 0.0289). Regarding patient-level factors, rural residence (defined by Rural-Urban Commuting Area codes), which accounted for 44.2% of the patient population, was significantly associated with lower telehealth utilization as compared to patients with urban residences, particularly for video appointments (OR 1.04, 95% CI 1.02 to 1.07; P &lt; 0.0001). Notably, the disparity in telehealth utilization between rural and urban populations was found to be less pronounced in 2021 as compared to 2020. Conclusions: Multivariable analysis across a multi-site, multi-regional cancer practice identified several factors associated with increased telehealth utilization. These included female physician provider type, referral-based campuses, and patients residing in urban settings. A detailed understanding of the factors that influence telehealth utilization – a method of care delivery which represents a “new normal” across many cancer practices – will be essential to enable continued equitable access to high-quality, high-impact, patient-centered cancer care.
The efficiency of anlotinib in osteosarcoma with chemoresistance: Exploratory therapy based on PDX models and next-generation sequencing.
Authors: Zuoyao Long, Zhanli Fu, Aikebaier Yunus, Yajie Lu, Minghui Li, Guojing Chen, Jing Li, Hong-Mei Zhang, Zhen Wang
Journal: Journal of Clinical Oncology (2022)

11527 Background: It’s urgent to find a new approach for the treatment of progressed osteosarcoma in neoadjuvant chemotherapy. Using patient-derived xenograft (PDX) models and next-generation sequencing (NGS), we have explored the efficiency of anlotinib in these patients. Methods: Frozen osteosarcoma tissues were used to establish PDX models. Ten samples of each PDX model were randomized to treatment or control group. The treatment group were gavaged at a volume of 0.1 ml/10g body weight for 4 weeks, while the control group were administered with vehicle at the same dose orally. Tumor volume and body weight were measured every 3 days, and the tumour were removed and weighed after 28 days. The number of mitotic cells and tumor necrosis rate were detected by Hematoxylin-Eosin (HE) staining. Immunohistochemistry (IHC) was used to evaluate the number of apoptotic cells and the expression of VEGFR-2, PDGFR-β, FGFR-1, c-Kit and their phosphorylated proteins, CD 31. Additionally, patients who had progressed during neoadjuvant chemotherapy (NAC) were treated with combination of anlotinib. After four cycles NAC, we performed salvage surgery and maintained with anlotinib. The change of tumor size was evaluated for tumor response. We used IHC and NGS to analyze the expression of drug targets. Results: 21 PDX models were established successfully from 43 samples. Tumor specimens from patients, who had pulmonary metastasis, local recurrence or chemoresistance, were easier to establish PDX models (P &lt; 0.001, P = 0.046, P = 0.013). Six models were selected randomly for anlotinib. After anlotinib administration, the tumor inhibition rates were 18.82%, 45.98%, 85.86%, 83.38%, 84.57% and 86.42%. Anlotinib could not only inhibit the mitosis, induce tumor cell apoptosis and necrosis, but also decrease the expression of drug targets. The expression of VEGFR-2, PDGFR-β and CD31 were positively associated with tumor response. Five patients had received anlotinib during NAC. Four patients had tumor regression (69.4%, 28%, 19%, 8.7%), including two with high expression of VEGFR-2 mRNA or/and PDGFR-β and one with medium expression. Conclusions: Based on the results of PDX models and NGS, we suggested that osteosarcoma with high expression of VEGFR-2 or/and PDGFR-β was sensitive to anlotinib, which was alternative for patients progressed during NAC.
Long-term oncologic outcomes and predictors of recurrence, cancer-specific and overall survival: Results from a high-volume center large consecutive series of robot assisted radical cystectomy with intracorporeal urinary diversion
Authors: G. Tuderti, R. Mastroianni, L. Misuraca, A. Bove, S. Guaglianone, U. Anceschi, A. Brassetti, M. Ferriero, M. Gallucci, G. Simone
Journal: European Urology (2022)
RARE-18. Pediatric craniopharyngioma; single center experience in 246 cases with different management modalities
Authors: Mohamed El Beltagy, Abdelrahman Enayet, Rana Sameh
Journal: Neuro-Oncology (2022)

Abstract PURPOSE: To report our experience with different craniopharyngioma management strategies done for 246 patients in a single institution during a period of 14 years. METHODS: The medical records of all children with the diagnosis of craniopharyngioma treated at Children's Cancer Hospital Egypt (CCHE-57357) during the period from July 2007 to December 2021 were retrospectively reviewed. RESULTS : our registry included 246 pediatric craniopharyngiomawith median age of 7.4 years old. The main strategies of management after initial surgery were follow up, radiotherapy or administration of intracystic interferone post ommaya insertion. The number of cases in each group were 92, 147,and three respectively. Three patients were not operated upon because of heavily calcified lesions, two of them received radiotherapy while the third was kept under follow up. Overall gross or near total total excision was achieved in 31.2 % , subtotal resection was the case in 42.1% while Ommaya insertion and biopsy was done in 21.1 % of cases. Total number of patients received radiotherapy initially or on progression was 195 patients( 78.9%). The five-year overall survival was 88% (95% CI 82.9 – 93.1) while 5- year progression free survival (PFS) was 49.2% (95% CI 41.2—57.2). The five-year PFS rates for patients in the follow up group versus radiotherapy group were 25.2% and 68.7% respectively (P&amp;lt; 0.0001). Beta catenin was positive in 76.4% of cases that were available for testing (123/161). CONCLUSION: management of craniopharyngioma should be individualized with the main objective is the quality of life. Conservative surgery which entails gross total safe resection whenever possible or lesser extent of resection followed by radiotherapy is the main strategy followed in our institution.
MEDB-27. Clinico-Radiological Outcomes in WNT-pathway Medulloblastoma: Retrospective Single Institutional Audit
Authors: Shakthivel Mani, Abhishek Chatterjee, Epari Sridhar, Ayushi Sahay, Neelam Shirsat, Aliasgar Moiyadi, Prakash Shetty, Girish Chinnaswamy, Vijay Patil, Archya Dasgupta, Nazia Bano, Tejpal Gupta
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Medulloblastoma (MB) is a heterogeneous disease comprising 4 molecular subgroups - wingless (WNT), sonic hedgehog, Group 3, and Group 4 tumors - with distinct developmental origins, diverse clinico-demographic characteristics, unique transcriptional profiles, and widely varying outcomes. WNT-MB is associated with the best outcomes (5-year survival &amp;gt;90%) prompting attempts at treatment de-escalation to reduce late toxicity. We undertook a clinical audit of WNT-MB patients treated at our tertiary-care comprehensive cancer centre. METHODS: Patients with molecularly confirmed WNT-MB treated with maximal safe resection followed by post-operative standard-of-care risk-stratified adjuvant radio(chemo)therapy were identified retrospectively via electronic search of the neuro-oncology database. Data regarding clinico-demographic characteristics, histo-molecular features, treatment details, patterns of failure, and survival outcomes was retrieved from electronic medical records and/or hospital case files. Time-to-event outcomes were analyzed using Kaplan-Meier methods and compared with the log-rank test. RESULTS: Between 2004 to 2018, a total of 65 patients of WNT-MB were registered at our institute. Five patients treated on a prospective clinical trial of therapy de-intensification were excluded leaving 60 patients that constitute the present study cohort. Median age at presentation was 12 years (inter-quartile range 9-18 years) with male preponderance (2:1). Six patients (1 post-operative mortality and 5 without adequate details of treatment or outcomes) were excluded from the survival analysis which was restricted to 54 patients. At a median follow-up of 66 months, Kaplan-Meier estimates of 5-year progression-free survival and overall survival were 87.9% and 92.8% respectively. Traditional high-risk features such as age, residual tumor (&amp;gt;1.5cm2) and leptomeningeal metastases (M+) did not emerge as significant prognostic factors for survival in this molecularly-characterized WNT-MB cohort. CONCLUSION: WNT-MB patients have excellent survival outcomes irrespective of traditional high-risk features suggesting the need for more tailored and refined risk-stratification with potential de-intensification of therapy. ACKNOWLEDGEMENTS: Brain Tumor Foundation (BTF) of India
Efficacy of dabrafenib-trametinib combination in <i>BRAF</i> V600E-mutated metastatic non–small cell lung cancer: Results of the IFCT-2004 BLaDE cohort.
Authors: Aurélie Swalduz, Michele Beau-Faller, David Planchard, Julien Mazieres, Sophie Bayle, Didier Debieuvre, Vincent Fallet, Margaux Geier, Alexis B Cortot, Sebastien Couraud, Catherine Daniel, Eric Pichon, Pascale Missy, Franck Morin, Virginie Westeel, Jean-Bernard Auliac, Remi Veillon
Journal: Journal of Clinical Oncology (2022)

9082 Background: BRAF V600E mutations occur up to 2% of advanced non-small cell lung (NSCLC). Dabrafenib-trametinib (D-T) combination was associated with improved OS rates in phase II study and was approved in the 1st-line setting and further. The IFCT-2004 BLaDE study reports the D-T combination efficacy in a large French real-world multicenter cohort of advanced BRAF V600E-mutated NSCLC. Methods: Patients (pts) with advanced NSCLC harboring BRAF V600E mutation diagnosed between 01.01.2016 and 31.12.2019 and treated with D-T combination (D 300 mg + T 2 mg daily) whatever the treatment line were included. Demographic, clinical, pathological data were collected as well as data of efficacy and reason of treatment discontinuation. The primary endpoint was 12 months-OS rate in pts receiving the D-T as 2nd-line or subsequent treatment (L2+). Results: 163 pts were included in 54 centers through 32 national testing labs: 50.3 % were female, 30.2% never-smokers, 95.1 % had adenocarcinoma and PDL1 was &gt; 1% in 78.2%. Median age was 68.3 years. At D-T initiation, 80.8 % of pts were PS 0/1, 93.9 % were stage IIIB/C ineligible for surgery or local therapy and IV, 20.9% had brain metastases and 27% received D+T as 1st line treatment (L1). At the data cutoff (30.06.2021), median (m) follow-up was 27.4 months [95% CI 22.2-31.9] and 47 pts (28.8%) remained on study treatment. 12 months-OS rate in pts receiving D+T in L2+ (n = 119) was 67.4% [95% CI 57.8-75.3] with a median progression-free survival (mPFS) of 10.4 months [95% CI 7.3-13.1]. In the 44 pts receiving D+T in L1, 12 months-OS rate was also 67.4% [95% CI 51.2-79.3] with a mPFS of 18.2 months [95% CI 7.7-21.3]. Objective response rates were 73.8% [95% CI 65.5 - 82.2] and 82.9% [95% CI 71.4 - 94.4], disease progression was observed as best response in 3.7% [95% CI 0.1 - 7.3] and 0% in L2+ and L1, respectively. Other efficacy results are detailed in the table. D-T discontinuation for toxicity was reported in 10.3% of pts. 51.2% and 43.7% of pts received subsequent treatment in L2+ and L1 respectively. For L2+ pts, subsequent treatments were immunotherapy (IO)-based in 37.2 % and chemotherapy in 58.3%. For L1 pts, subsequent treatments were (IO)-based in 42.9% and chemotherapy in 42.7%. Conclusions: Our series confirms significant efficacy of D-T combination in BRAF V600E-mutated metastatic NSCLC. These results in real-world conditions are consistent with registration studies but also support its use in 1st line setting. [Table: see text]
Three-year disease-free survival in randomized trials of chemotherapy and HER2-targeted therapy: A meta-analysis.
Authors: Abhenil Mittal, Faris Tamimi, Consolacion Molto, Nicholas Meti, Laith Al-Showbaki, Brooke Wilson, Eitan Amir
Journal: Journal of Clinical Oncology (2022)

579 Background: The Katherine trial reported a 3-year invasive disease-free survival (DFS) of 77% in patients not achieving pathological complete response (pCR) and continuing on adjuvant trastuzumab. Case series suggest better outcomes and data support that some patients with residual disease have similar outcomes to those with pCR (Steenbruggen et al). The absolute benefit of adjuvant trastuzumab emtansine (T-DM1) would be smaller in patients with favourable outcomes despite residual disease. As such, a more precise estimate of 3-year DFS is needed for treatment planning. Methods: We reviewed reports of randomized trials of neoadjuvant chemotherapy and HER2-directed therapy and extracted the 3-year DFS, a validated surrogate endpoint in HER2-positive early-stage breast cancer. Data were extracted for patients with residual disease and with pCR. The mean 3-year DFS weighted by study sample size was calculated. Meta-regression comprising linear regression weighted by sample size (mixed effects) was performed to explore associations between 3-year DFS and trial-level patient, disease and treatment factors and changes in 3-year DFS over time. Quantitative significance was explored using methods described by Burnand et al. Results: Eleven studies comprising 3908 patients were included in the analysis. The mean 3-year DFS for patients with pCR and for residual disease was 90.1% and 80.0%, respectively. DFS improved over time. For trials whose final year of accrual was after 2010, mean 3-year DFS for residual disease was 84.7% compared to 78.0% for trials completing accrual before that time (p&lt;0.001). In a subgroup analysis of patients with residual disease, those receiving dual HER2-targeted therapy in the neoadjuvant setting had a 3-year DFS of 85.3% compared to 73.3% for those receiving only trastuzumab (p&lt;0.001). Meta-regression results for residual disease are shown in the Table. Positive quantitative significance was observed for final year of accrual, ER-expression, dual anti-HER2 therapy and concurrent vs sequential anti-HER2 therapy. Negative quantitative significance was observed for larger clinical tumor size and nodal involvement. Conclusions: 3-year DFS for patients with residual disease and HER2-targeted therapy is better than reported in the Katherine trial and has improved over time, possibly due to increased use of dual HER2-targeted therapy in the neoadjuvant setting. In this context, the absolute benefit of adjuvant T-DM1 may be smaller than anticipated. [Table: see text]